Hydroxyurea (Hydroxycarbamide)

Indications

Hydroxyurea (Hydroxycarbamide) is used for: Chronic myeloid leukaemia, Psoriasis, Myeloproliferative disorders, Sickle-cell disease, Essential thrombocythemia, AIDS

Adult Dose

Solid Tumors Intermittent Therapy: 80 mg/kg PO q3day, OR Continuous Therapy: 20-30 mg/kg PO qDay Head & Neck Tumors Concomitant therapy with irradiation 80 mg/kg PO q3days Begin 7 days prior to initiation of irradiation Chronic Myelocytic Leukemia, Resistant Continuous Therapy: 20-30 mg/kg PO qDay Sickle Cell Disease Start: 15 mg/kg/day as single dose; monitor patient’s blood count every two weeks Titrate by 5 mg/kg/day q12wk Dose is not increased if blood counts are between acceptable range and toxic Not to exceed 35 mg/kg/day Discontinue therapy until hematologic recovery if blood counts are considered toxic; may resume treatment after reducing dose by 2.5 mg/kg/day from dose associated with hematological toxicity Thrombocythemia, Essential 15 mg/kg PO qDay Titrate to control platelets & maintain WBC count

Child Dose

Oral Sickle-cell disease Child: 1-18 yr: 10-20 mg/kg/day, increased by 5 mg/kg/day every 12 wk according to response and blood counts.

Renal Dose

Renal impairment: Dose reduction may be needed.

Administration

Contra Indications

Severe bone-marrow suppression, severe anaemia, WBC <3000/mm3 or platelet count <100,000/mm3. Pregnancy and lactation. Hypersensitivity.

Precautions

Regular monitoring of uric acid concentrations, blood counts, renal and hepatic function is recommended. Prior irradiation therapy. Elderly. Avoid use of live vaccines. Lactation: excreted in breast milk, do not nurse

Pregnancy-Lactation

Interactions

Impairs immune response to vaccines; possible infection with live vaccines, zidovudine, zalcitabine. May alter action of oral anticoagulants and phenytoin. Potentially Fatal: Fluorouracil may increase potential for neurotoxicity. Modulates metabolism and cytotoxicity of cytarabine. May precipitate didanosine- or stavudine-induced pancreatitis, hepatotoxicity or neuropathy.

Adverse Effects

Side effects of Hydroxyurea (Hydroxycarbamide) : GI disturbances, Nausea, Vomiting, Constipation, Diarrhea, Hyperuricemia, Renal failure, Rash, Hyperpigmentation. Pulmonary oedema, dermatological reactions, headache, dizziness. Disorientation, drowsiness, hallucinations, convulsions, alopecia. Potentially Fatal: Bone marrow suppression.

Mechanism of Action

Hydroxycarbamide causes inhibition of DNA synthesis during the S-phase of cell division by acting as a ribonucleotide reductase inhibitor resulting to cell death. It is S-phase specific.